Wolters Kluwer Health may email you for journal alerts and information, but is committed
to maintaining your privacy and will not share your personal information without
your express consent. For more information, please refer to our Privacy Policy.

Abstract

Background: There is intense interest in the role of programmed death 1 (PD-1) in causing persistent T-cell dysfunction in HIV infection. However, the impact of HIV infection and antiretroviral treatment (ART) on the expression of PD-1 on T cells is still poorly defined.

Methods: PD-1 was measured longitudinally in a cohort of recently HIV-infected individuals (n = 121) who started ART early (<6 months after infection) vs. later (≥2 years after infection). PD-1 was also measured cross-sectionally in a diverse cohort of chronically HIV-infected adults (n = 206).

Results: PD-1 expression levels were high on CD8+ T cells during early HIV infection. PD-1 levels increased on both CD4+ and CD8+ T cells populations in those who delayed therapy (11 and 10%/year, respectively). PD-1 levels declined and were similar in those treated early vs. late after 1 year of ART. In both cohorts, PD-1 expression on CD4+ T cells was associated with CD4+ T-cell activation (CD38+HLA-DR+) and inversely with CD4+ cell count. In contrast, PD-1 expression on CD8+ T cells was most strongly associated with CD8+ T-cell activation and with plasma viral load in viremic individuals.

Conclusion: Across two large cohorts of untreated and treated individuals, we found consistent associations between HIV RNA levels, CD8+ T-cell activation and PD-1 expression on CD8+ T cells. In contrast, CD4+ T-cell counts and CD4+ T-cell activation were more consistent correlates of PD-1 expression on CD4+ T cells. PD-1 expression appears to be driven by both direct antigen and homeostatic pathways.

Enter and submit the email address you registered with. An email with instructions to reset your password will be sent to that address.

Email:

Password Sent

Link to reset your password has been sent to specified email address.

Remember me

What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
computer.

To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.

What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.